Research:
Molecular Mechanisms of Mitosis
The long term goal of my research is to understand the mechanisms regulating mitosis. These mechanisms are fundamental to reproduction, development, and human health. Because the molecular biology of mitosis is conserved from fungi to humans, my lab utilizes fungi as model research organisms to gain insight into the essential nature of mitosis. My lab currently investigates two major areas.
1) Function of the Anaphase-Promoting Complex/Cyclosome (APC/C) in Aspergillus nidulans. APC/C is a conserved ubiquitin ligase which regulates exit from mitosis by controlling the ubiquitin-dependent proteolysis of mitotic proteins. APC/C also functions in G2 phase in A. nidulans, although little is known about APC/C regulation or function in G2. Questions my lab is addressing include the role of ubiquitin conjugating enzymes and Fizzy-related proteins in APC/C regulation and function, with emphasis on the G2 to M transition .
2) Functional Genomics of Mitosis. Studies of filamentous fungi have pioneered progress in Genetics and Cell Biology for more than a half century. The recent explosion in the number of available fungal genome sequences has opened the door to comparative genomics of all aspects of fungal biology. My lab is using this information to study regions of the genome important for mitosis, for example, centromeres and the proteins that bind to them.
My laboratory hopes to utilize fungal genetics and biology to gain knowledge and understanding that will be of general interest to the molecular and cellular biology community. Individuals interested in undergraduate, graduate, and post-graduate research positions are encouraged to contact me at pmmira00@uky.edu.
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Selected Publications:
Foster, S. and P.M. Mirabito. 1998. Inactivation of vitamin B6 by hydroxyurea in Aspergillus culture media. Fungal Genetics Newsletter 45:11-12.
Wu, L., S.A. Osmani and P.M. Mirabito. 1998. A role for NIMA in the nuclear localization of Cyclin B in Aspergillus nidulans. J. Cell Biol. 141:1575-1587.
Lies, C.M., J. Cheng, S.W. James, M. O'Connell, N.R. Morris and P.M. Mirabito. 1998. BIMA, a component of the Aspergillus anaphase promoting complex/cyclosome, is required for a G2 checkpoint blocking entry into mitosis in the absence of NIMA function. J. Cell Sci. 111:1453-1465.
Wolkow,T.D., Mirabito,P.M., Venkatram,S., and Hamer,J.E. (2000). Hypomorphic bimA (APC3) alleles cause errors in chromosome metabolism that activate the DNA damage checkpoint blocking cytokinesis in Aspergillus nidulans. Genetics 154, 167-179.
Mirabito, P.M. and S. A. Osmani. (2004) The early impact of genetics on our understanding of cell cycle regulation in Aspergillusnidulans. Fungal Genetics and Cell Biology 41: 401-410.
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